This project is concerned with a comparative analysis of ionic current channels in nerve and heart cell membranes and the relationship of these channels to electrical excitability, with a Particular emphasis on potassium ion channels in both preparations and the effects of various ionic blockers on these channels. During the past year the primary experimental preparations which have been used are squid giant axons and chick embryonic heart cells. This work has focused recently on the delayed rectifier potassium channel, IK, in squid axons. A major finding has been that this channel is modulated by the intracellular application of adenosine triphosphate (ATP). Specifically, the voltage dependence of the inactivation of IK is shifted in the hyperpolarizing direction by ATP, which suggest that the basal ATP level regulates excitability of the squid axon at rest. The effect is probably mediated by phosphorylation of a subunit of the membrane protein which comprises the IK channel, which suggests that the channel protein, or part of the channel protein, may be amenable to isolation and purification by biochemical techniques.